If you want to know all about calcium’s effects on synapse dynamics in the hippocampus, your going to want to check out the stuff by Malenka and Nicoll but I think maybe the paper you were thinking of was the Sabatini & Svoboda Neuron paper a couple of years back (PMID 11832230)???? Just a guess…

Regarding the original posting, it seems like SR141716 is a pretty sloppy antagonist (at least judging from the Nicoll and Algers papers). I would be very surprised if it makes it past phase III. I wonder when the public is going to catch on to the fact these magic little pills perscribed by their Doctor is just some scientists half assed attempt to get rich quick…

There are other, more technical reasons that we would want to consider too… In the case of THC, it is a broad spectrum agonist for several receptors, including CB2 (and I’m sure other cannabinoid receptors that I’m not aware of). Surely, a CB1 antagonist will not be able to account for all of the diverse phenomena that THC produces. Also, the binding constants governing the receptor-ligand interaction matter enormously. For example, the CB1 antagonist might not bind the receptor as strongly as THC. Even though THC is an agonist, the receptors are only the first step in a complex signalling cascade. Low levels of antagonist action and high levels of agonist action might result in the same downstream effects. (Wasn’t there some LTP paper that showed that low levels of cytosolic Ca++ and high levels of Ca++ resulted in LTP but medium levels resulted in LTD?)

A Dogg: We know it’s an antagonist; my reasoning was just that if a cannabinoid agonist affects cognitive processing seriously enough that people are afraid of it, then an antagonist of the same receptor may have equally profound effects, although perhaps harder to detect, and therefore people should treat it with caution.